MK-2206 dihydrochloride (Synonyms: MK-2206,MK2206,MK 2206) |
| カタログ番号GC16304 |
アロステリックAkt阻害剤
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1032350-13-2
Sample solution is provided at 25 µL, 10mM.
MK-2206 dihydrochloride is an orally active allosteric Akt inhibitor used in treatment of solid tumors.[1]
IIn vitro experiment it shown that MK-2206 is equally potent toward purified recombinant human Akt1 and Akt2 enzyme with IC50 of 5 nmol/L and 12 nmol/L, respectively; and approximately 5-fold less potent against human Akt3 (IC50, 65 nmol/L). MK-2206 potently inhibited the cell growth of Ras wild-type (WT) cell lines (A431, HCC827, and NCI-H292 with IC50s of 5.5, 4.3, and 5.2 μmol/L, respectively. The combination of 2.5 μmol/L erlotinib and 3 μmol/L MK-2206 or higher obviously activated the caspase.[1] In vitro, Akt inhibitor (MK 2206 dihydrochloride, 2.5 nM) reduces the effects of anti-microRNA-320a on the apoptosis of MDA-MB-231 cells.[2] In vitro, treatment with 0.1 and 1 μM for 48 h MK-2206 reduced the expression p-Akt in all pancreatic cancer cell lines suggesting that MK-2206 inhibited Akt phosphorylation in pancreatic cancer cells.[3] In vitro the colony formation assay confirmed that 1 μM of MK-2206 significantly inhibited the proliferation of SGC-7901 cells.[4]
In vivo test displayed it that treatment with 120 mg/kg MK-2206 orally 2 hours after erlotinib (50 mg/kg), and tumors were isolated 14 hours after erlotinib administration to verify the inhibition of phospho-Akt for the PI3K pathway and phospho-Erk for the Ras/Erk pathway. In vivo efficacy studies it demonstrated that the antitumor efficacy of MK-2206 with once a week at 360 mg/kg intermittently dosing was quite similar to the efficacy of three times a week at 120 mg/kg dosing when MK-2206 was combined with erlotinib.[1].
References:
[1]. Hirai H, et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther. 2010 Jul;9(7):1956-67.
[2]. Guan J, et al. MicroRNA 320a suppresses tumor cell growth and invasion of human breast cancer by targeting insulin like growth factor 1 receptor. Oncol Rep. 2018 Aug;40(2):849-858.
[3]. Wang Z, et al. Akt inhibitor MK-2206 reduces pancreatic cancer cell viability and increases the efficacy of gemcitabine. Oncol Lett. 2020 Mar;19(3):1999-2004.
[4]. Jin P, et al. MK-2206 co-treatment with 5-fluorouracil or doxorubicin enhances chemosensitivity and apoptosis in gastric cancer by attenuation of Akt phosphorylation. Onco Targets Ther. 2016 Jul 19;9:4387-96.
| Cell experiment [1]: | |
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Cell lines |
NCI-H292 NSCLC cells |
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Preparation Method |
Cells were treated with MK-2206 (0, 0.3, 1, and 3 μmol/L) in the presence or absence of erlotinib (0, 0.6, 2.5, 10, and 20 μmol/L) for 48 h. Apoptosis was evaluated by measuring the caspase-3/7 activity. |
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Reaction Conditions |
MK-2206 (0, 0.3, 1, and 3 μmol/L), 48h |
|
Applications |
Caspase activation became apparent at 2.5 μmol/L erlotinib and 3 μmol/L MK-2206 or higher. |
| Animal experiment [2]: | |
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Animal models |
female nu/nu mice |
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Preparation Method |
1 × 107 ZR75-1 breast cancer cells were inoculated in the mammary fat pads of female nu/nu mice. Mice were subcutaneously implanted with 17β-estradiol pellets. Mice bearing ZR75-1 xenografts were randomized into 3 groups (vehicle, MK-2206 240 mg/kg, or 480 mg/kg, n = 5–6). Tumor measurements were followed to assess antitumor efficacy, and RPPA was utilized to assess the effect on cell signaling as described above. |
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Dosage form |
240 mg/kg, or 480 mg/kg, p.o. |
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Applications |
MK-2206 (240 mg/kg, or 480 mg/kg) inhibits tumor growth in ZR75-1 xenografts. |
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References: [1]. Hirai H, et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther. 2010 Jul;9(7):1956-67. [2]. Xing Y, et al. Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation. Breast Cancer Res. 2019 Jul 5;21(1):78. |
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| Cas No. | 1032350-13-2 | SDF | |
| 同義語 | MK-2206,MK2206,MK 2206 | ||
| Chemical Name | 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one;dihydrochloride | ||
| Canonical SMILES | C1CC(C1)(C2=CC=C(C=C2)C3=C(C=C4C(=N3)C=CN5C4=NNC5=O)C6=CC=CC=C6)N.Cl.Cl | ||
| Formula | C25H21N5O.2HCl | M.Wt | 480.39 |
| 溶解度 | ≥ 12.01mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0816 mL | 10.4082 mL | 20.8164 mL |
| 5 mM | 0.4163 mL | 2.0816 mL | 4.1633 mL |
| 10 mM | 0.2082 mL | 1.0408 mL | 2.0816 mL |
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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